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In this article, thermal properties, molecular dynamics, crystallization kinetics, and intermolecular interactions in pure naproxen (NAP), its amide (NH 2 -NAP), and four esters (methyl, Met-NAP; isopropyl, Iso-NAP; hexyl, Hex-NAP; and benzyl, Ben-NAP) have been investigated using differential scanning calorimetry as well as broadband dielectric and Fourier transform infrared spectroscopies. We found that the modification of the NAP molecule by substituting a hydrogen atom from the hydroxyl group strongly inhibits the crystallization tendency of this active pharmaceutical ingredient (API) and simultaneously increases its glass forming ability (GFA). In this context, it is worthwhile to stress that pure naproxen and its amide crystallized very quickly, regardless of the cooling rate. Therefore, these compounds cannot be classified as good glass-formers. On the other hand, ester derivatives of API can be easily vitrified. Moreover, dielectric measurements revealed that with an increasing molecular weight of the substituent, the rate of crystallization process slows down significantly. Consequently, Ben-NAP was characterized by the highest GFA among all investigated API esters. Comprehensive FTIR studies clearly indicated that the strong tendency to create dimeric structures in the nonmodified NAP and NH 2 -NAP is responsible for their enhanced crystallization. At the first sight, our results stay in contrast to most literature data, showing that H-bonds favor the glass formation ability. However, this effect is usually observed for the materials, which form extensive multidirectional hydrogen bonds and associates. In NAP and NH 2 -NAP, the situation is much different, since both compounds exist mainly as dimers. Therefore, one can postulate that specific intermolecular interactions are an important parameter determining the GFA of different materials, including APIs.

In this paper, we investigated the molecular mobility and physical stability of amorphous bicalutamide, a poorly water-soluble drug widely used in prostate cancer treatment. Our broadband dielectric spectroscopy measurements and differential scanning calorimetry studies revealed that amorphous BIC is a moderately fragile material with a strong tendency to recrystallize from the amorphous state. However, mixing the drug with polymer polyvinylpyrrolidone results in a substantial improvement of physical stability attributed to the antiplasticizing effect governed by the polymer additive. Furthermore, IR study demonstrated the existence of specific interactions between the drug and excipient. We found out that preparation of bicalutamide-polyvinylpyrrolidone mixture in a 2-1 weight ratio completely hinder material recrystallization. Moreover, we determined the time-scale of structural relaxation in the glassy state for investigated materials. Because molecular mobility is considered an important factor governing crystallization behavior, such information was used to approximate the long-term physical stability of an amorphous drug and drug-polymer systems upon their storage at room temperature. Moreover, we found that such systems have distinctly higher water solubility and dissolution rate in comparison to the pure amorphous form, indicating the genuine formulation potential of the proposed approach.